What is the evidence that radiotherapy, either pre-operative or post-operative, decreases local recurrence or improves survival in retroperitoneal sarcomas?

Introduction

Retroperitoneal Sarcomas (RPS) are relatively uncommon, constituting 10-15% of all Soft Tissue Sarcomas (STS). Patients usually present in their fifties, although the age range can be broad. Both males and females are equally affected. The most common histologic types of RPS are liposarcomas, leiomyosarcomas and pleomorphic undifferentiated sarcomas. RPS typically produce few symptoms until they are large enough to compress or invade surrounding structures. Most cases come to attention as an incidentally discovered abdominal mass in an asymptomatic or minimally symptomatic patient. Most tumours are already large at presentation (median size 15cm).

Rationale for adding Radiotherapy

Surgical resection has traditionally been the only potentially curative treatment of localised RPS. However, in contrast to Extremity STS where the most common site of first recurrence is a distant site, the primary pattern of failure after resection of a RPS is local. Five year local recurrence rates after complete resection of a RPS is around 50% and local recurrence is the site of first failure in 90% of cases. These high relapse rates have prompted investigation of combined modality approaches such as radiation therapy.

Unfortunately, with RPS being an “Orphan Disease” there are no randomised trials of surgery with and without External beam radiation therapy (EBRT). There was one trial Z9031 initiated by the American College of Surgeons Oncology Group (ASCOG) randomising to preoperative radiotherapy (RT) vs Surgery alone. This closed prematurely due to slow patient accrual. At the time of writing, the European Organisation for Research and Treatment of Cancer (EORTC) protocol 62092 is preparing to accrue patients for a phase III randomised controlled trial comparing preoperative RT plus surgery vs surgery alone for patients with RPS. However, the results of this study will not be available for many years to come.

There are many retrospective studies, mainly institutional reports which have shown improved local control benefit. Two large studies [1][2] have shown that adjuvant RT improves local recurrence free survival significantly. Recent large population based multi-institutional studies such as SEER database analysis which have looked at overall survival benefit have however been conflicting. A smaller SEER analyisis[3] showed no survival benefit, where as an analysis with larger number showed a survival benefit.[4] Another SEER analysis[5] showed survival benefit in malignant fibrous histiocytoma (MFH) subgroup only.

Newer Radiotherapy techniques

There is some evidence that newer RT techniques such as Intraoperative Electron beam therapy (IORT) may be beneficial, but this is usually confined to few centres worldwide and not available in Australia. There is some promise with the use of Intensity modulated radiation therapy (IMRT) in RPS, but still in early stages and may take some time for results to come.

In patients with non-metastatic retroperitoneal sarcomas, adding radiotherapy to surgery is appropriate to further improve local control. When offered, pre-operative radiotherapy is preferable to post-operative radiotherapy.